Professor Thomas Huber
Areas of expertise
- Physical Organic Chemistry 030505
- Medical Biochemistry: Proteins And Peptides (Incl. Medical Proteomics) 110106
- Structural Chemistry And Spectroscopy 030606
- Medicinal And Biomolecular Chemistry 0304
- Organic Chemistry 0305
- Computer Software 0803
- Bioinformatics 060102
Biography
Thomas Huber received his Diploma of Chemistry from the Technical University Munich and completed his PhD at ETH-Zurich.
He has since held positions in physical chemistry at ETH-Zurich (1997), in the Supercomputer Facility at ANU (1998-2000), in the Department of Mathematics at UQ (2001-2005) and in the School of Molecular Bioscience at UQ (2006-2010). He moved to ANU as ARC Future Fellow (2010-2014) before being appointed Professor at the Research School of Chemistry.
Researcher's projects
N. Dixon, T. Huber, K. Ozawa, M. Tehei, Mapping protein contacts and conformational changes in macromolecular assemblies (DP0984797 2009-2013)
G. Otting and T. Huber, New fragment-based drug design technology by NMR spectroscopy (DP0985549 2009-2011)
T. Huber, 3D structure determination of biomolecular assemblies from sparse data (FT0991709 2010-2014)
T. Huber, G. Otting, B. Graham, 3D structure determination of biomolecular assemblies from sparse data of different length scales (DP120100561 2012-2014)
Past student projects
B. Gladwin, Long timescale path integral molecular dynamics from equations of motion. PhD 2007
D. Mouradov, Application of a bioinformatic/biochemical hybrid approach to determine the structure of protein complexes and multi domain proteins. PhD 2008
C. Schmitz, Computational study of proteins with paramagnetic NMR: Automatic assignments of spectral resonances, determination of protein-protein and protein-ligand complexes, and structure determination of proteins. PhD 2009
Publications
- Abdelkader, E, Qianzhu, H, Tan, Y et al. 2021, 'Genetic Encoding of N6-(((Trimethylsilyl)methoxy)carbonyl)- l -lysine for NMR Studies of Protein-Protein and Protein-Ligand Interactions', Journal of the American Chemical Society, vol. 143, no. 2, pp. 1133-1143.
- Koehler Leman, J, Weitzner, B, Lewis, S et al. 2020, 'Macromolecular modeling and design in Rosetta: recent methods and frameworks', Nature Methods: techniques for life scientists and chemists, vol. 17, pp. 665-680.
- Qianzhu, H, Welegedara, A, Williamson, H et al. 2020, 'Genetic Encoding of para-Pentafluorosulfanyl Phenylalanine: A Highly Hydrophobic and Strongly Electronegative Group for Stable Protein Interactions', Journal of the American Chemical Society, vol. 142, no. 41, pp. 17277-17281.
- Yardeni, E, Bahrenberg, T, Stein, R et al. 2019, 'Probing the solution structure of the E. coli multidrug transporter MdfA using DEER distance measurements with nitroxide and Gd(III) spin labels', Scientific Reports, vol. 9.
- Nitsche, C, Onagi, H, Quek, J et al 2019, 'Biocompatible Macrocyclization between Cysteine and 2-Cyanopyridine Generates Stable Peptide Inhibitors', Organic Letters, vol. 21, no. 12, pp. 4709-4712.
- Bahramzadeh, A, Huber, T & Otting, G 2019, 'Three-Dimensional Protein Structure Determination Using Pseudocontact Shifts of Backbone Amide Protons Generated by Double-Histidine Co2+-Binding Motifs at Multiple Sites', Biochemistry, vol. 58, no. 30, pp. 3243-3250.
- Welegedara, A, Adams, L, Huber, T et al 2018, 'Site-Specific Incorporation of Selenocysteine by Genetic Encoding as a Photocaged Unnatural Amino Acid', Bioconjugate Chemistry, vol. 29, no. 7, pp. 2257-2264.
- Bahramzadeh, A, Jiang, H, Huber, T et al 2018, 'Two Histidines in an α�Helix: A Rigid Co2+�Binding Motif for PCS Measurements by NMR Spectroscopy', Angewandte Chemie International Edition, vol. 57, no. 21, pp. 6226-6229pp.
- Pilla, K, Otting, G & Huber, T 2017, '3D Computational Modeling of Proteins Using Sparse Paramagnetic NMR Data', in Jonathan Keith (ed.), Methods in Molecular Biology - Bioinformatics: Structure, Function and Applications, Humana Press Inc., USA, pp. 3-21pp.
- Welegedara, A, Yang, Y, Lee, M et al 2017, 'Double-Arm Lanthanide Tags Deliver Narrow Gd3+-Gd3+ Distance Distributions in Double Electron-Electron Resonance (DEER) Measurements', Chemistry, A European Journal, vol. 23, no. 48, pp. 11694-11702.
- Nitsche, C, Mahawaththage Don, M, Becker, W et al 2017, 'Site-selective tagging of proteins by pnictogen-mediated self-assembly', Chemical Communications, vol. 53, no. 79, pp. 10894-10897pp.
- Pilla, K, Otting, G & Huber, T 2017, 'Protein Structure Determination by Assembling Super-Secondary Structure Motifs Using Pseudocontact Shifts', Structure, vol. 25, no. 3, pp. 559-568.
- Pan, B, Yang, F, Ye, Y et al 2016, '3D structure determination of a protein in living cells using paramagnetic NMR spectroscopy', Chemical Communications, vol. 52, no. 67, pp. 10237-10240.
- Yang, Y, Huang, F, Huber, T et al 2016, 'Site-specific tagging proteins with a rigid, small and stable transition metal chelator, 8-hydroxyquinoline, for paramagnetic NMR analysis', Journal of Biomolecular NMR, vol. 64, no. 2, pp. 103-113.
- Pilla, K, Otting, G & Huber, T 2016, 'Pseudocontact Shift-Driven Iterative Resampling for 3D Structure Determinations of Large Proteins', Journal of Molecular Biology, vol. 428, no. 2, pp. 522-532.
- Chen, J, Yang, Y, Zhang, L et al. 2016, 'Analysis of the solution conformations of T4 lysozyme by paramagnetic NMR spectroscopy', Physical Chemistry Chemical Physics, vol. 18, no. 8, pp. 5850-5859.
- Chen, W, Nitsche, C, Pilla, K et al 2016, 'Sensitive NMR Approach for Determining the Binding Mode of Tightly Binding Ligand Molecules to Protein Targets', Journal of the American Chemical Society, vol. 138, no. 13, pp. 4539-4546.
- Porter, J, Boon, P, Murray, T et al 2015, 'Directed evolution of new and improved enzyme functions using an evolutionary intermediate and multidirectional search', ACS chemical biology, vol. 10, no. 2, pp. 611-621.
- Chen, W, Kuppan, K, Lee, M et al. 2015, 'O-tert-Butyltyrosine, an NMR Tag for High-Molecular-Weight Systems and Measurements of Submicromolar Ligand Binding Affinities', Journal of the American Chemical Society, vol. 137, no. 13, pp. 4581-4586.
- Pilla, K, Leman, J, Otting, G et al. 2015, 'Capturing Conformational States in Proteins Using Sparse Paramagnetic NMR Data', PLOS ONE (Public Library of Science), vol. 10, no. 5, pp. e0127053-e0127053.
- Zhao, Y, Soh, T, Chan, K et al 2015, 'Flexibility of NS5 methyltransferase-polymerase linker region is essential for dengue virus replication', Journal of Virology, vol. 89, no. 20, pp. 10717-10721.
- Shishmarev, D, Wang, Y, Mason, C et al. 2014, 'Intramolecular binding mode of the C-terminus of Escherichia coli single-stranded DNA binding protein determined by nuclear magnetic resonance spectroscopy', Nucleic Acids Research, vol. 42, no. 4, pp. 2750-2757.
- Skarshewski, A, Stanton-Cook, M, Huber, T et al 2014, 'uPEPperoni: an online tool for upstream open reading frame location and analysis of transcript conservation', BMC Bioinformatics, vol. 15, no. 36, pp. 1-6.
- Edwards, D, Huber, T, Hussain, S et al 2014, 'Determining the oligomeric structure of proteorhodopsin by Gd3+-based pulsed dipolar spectroscopy of multiple distances', Structure, vol. 22, no. 11, pp. 1677-1686.
- Milthorpe, J, Rendell, A P & Huber, T 2014, 'PGAS-FMM: Implementing a distributed fast multipole method using the X10 programming language', Concurrency and Computation: Practice and Experience, vol. 26, issue 3, pp. 712-727. doi:10.1002/cpe.3039
- Matalon, E, Huber, T, Hagelueken, G et al 2013, 'Gadolinium(III) spin labels for high-sensitivity distance measurements in transmembrane helices', Angewandte Chemie International Edition, vol. 52, no. 45, pp. 11831-11834.
- Loh, C, Ozawa, K, Tuck, K et al 2013, 'Lanthanide tags for site-specific ligation to an unnatural amino acid and generation of pseudocontact shifts in proteins', Bioconjugate Chemistry, vol. 24, no. 2, pp. 260-268.
- Kaminker, I, Tkach, I, Manukovsky, N et al 2013, 'W-band orientation selective DEER measurements on a Gd3+/nitroxide mixed-labeled protein dimer with a dual mode cavity', Journal of Magnetic Resonance, vol. 227, pp. 66-71.
- Jergic, S, Horan, N, Elshenawy, M et al 2013, 'A direct proofreader-clamp interaction stabilizes the Pol III replicase in the polymerization mode', The EMBO Journal, vol. 32, no. 9, pp. 1322-1333.
- Li, J, Pilla, K.B, Li, Q et al 2013, 'Magic angle spinning NMR structure determination of proteins from pseudocontact shifts', Journal of the American Chemical Society, vol. 135, no. 22, pp. 8294-8303.
- Ozawa, K, Horan, N, Robinson, A et al 2013, 'Proofreading exonuclease on a tether: the complex between the E. coli DNA polymerase III subunits alpha, epsilon, theta and beta reveals a highly flexible arrangement of the proofreading domain', Nucleic Acids Research, vol. 41, no. 10, pp. 5354-5367.
- Yagi, H, Pilla, K, T, Maleckis, A et al 2013, 'Three-dimensional protein fold determination from backbone amide pseudocontact shifts generated by lanthanide tags at multiple sites', Structure, vol. 21, no. 6, pp. 883-890.
- Banerjee, D, Yagi, H, Huber, T et al 2012, 'Nanometer-range distance measurement in a protein using Mn2+ tags', Journal of Physical Chemistry Letters, vol. 3, no. 2, pp. 157-160.
- Loscha, K, Herlt, A, Qi, R et al 2012, 'Multiple-site labeling of proteins with unnatural amino acids', Angewandte Chemie International Edition, vol. 51, no. 9, pp. 2243-2246.
- Schmitz, C, Vernon, R, Otting, G et al 2012, 'Protein structure determination from pseudocontact shifts using ROSETTA', Journal of Molecular Biology, vol. 416, no. 5, pp. 668-677.
- Kaminker, I, Yagi, H, Huber, T et al 2012, 'Spectroscopic selection of distance measurements in a protein dimer with mixed nitroxide and Gd3+ spin labels', Physical Chemistry Chemical Physics, vol. 14, no. 13, pp. 4355-4358.
- Ding, T, Middelberg, A, Falconer, R et al 2012, 'Far-infrared spectroscopy analysis of linear and cyclic peptides, and lysozyme', Vibrational Spectroscopy, vol. 61, pp. 144-150.
- Graham, B, Loh, C, Swarbrick, J et al 2011, 'DOTA-amide lanthanide tag for reliable generation of pseudocontact shifts in protein NMR spectra', Bioconjugate Chemistry, vol. 22, no. 10, pp. 2118-2125.
- Ding, T, Huber, T, Middelberg, A et al 2011, 'Characterization of low-frequency modes in aqueous peptides using far-infrared spectroscopy and molecular dynamics simulation', Journal of Physical Chemistry A, vol. 115, no. 42, pp. 11559-11565.
- Jia, X, Maleckis, A, Huber, T et al 2011, '4,4 '-Dithiobisdipicolinic Acid: A Small and Convenient Lanthanide Binding Tag for Protein NMR Spectroscopy', Chemistry, A European Journal, vol. 17, no. 24, pp. 6830-6836.
- Swarbrick, J, Ung, P, Su, X et al. 2011, 'Engineering of a bis-chelator motif into a protein α-helix for rigid lanthanide binding and paramagnetic NMR spectroscopy', Chemical Communications, vol. 47, no. 26, pp. 7368-7370.
- Yagi, H, Banerjee, D, Graham, B et al 2011, 'Gadolinium tagging for high-precision measurements of 6 nm distances in protein assemblies by EPR', Journal of the American Chemical Society, vol. 133, no. 27, pp. 10418-10421.
- Jia, X, Yagi, H, Su, X et al. 2011, 'Engineering [Ln(DPA)3]3- binding sites in proteins: a widely applicable method for tagging proteins with lanthanide ions', Journal of Biomolecular NMR, vol. 50, no. 4, pp. 411-420.
- de la Cruz, L, Nguyen, T, Ozawa, K et al 2011, 'Binding of low molecular weight inhibitors promotes large conformational changes in the dengue virus NS2B-NS3 protease: fold analysis by pseudocontact shifts', Journal of the American Chemical Society, vol. 133, no. 47, pp. 19205-19215.
- Nguyen T. H. D.; Ozawa K.; Stanton-Cook M.; Barrow R.; Huber T.; Otting G.; 2011, Generation of pseudocontact shifts in protein NMR spectra with a genetically encoded cobalt(II)-binding amino acid, Angewandte Chemie International Edition, 50, 692-694.
- Ding, T, Li, R, Zeitler, J et al 2010, 'Terahertz and far infrared spectroscopy of alanine-rich peptides having variable ellipticity', Optics Express, vol. 18, no. 26, pp. 27431-27444.
- Man, B, Su, X, Liang, H et al. 2010, '3-Mercapto-2,6-Pyridinedicarboxylic Acid: A Small Lanthanide-Binding Tag for Protein Studies by NMR Spectroscopy', Chemistry, A European Journal, vol. 16, no. 12, pp. 3827-3832.
- Yagi, H, Loscha, K, Su, X et al. 2010, 'Tunable paramagnetic relaxation enhancements by [Gd(DPA)3]3- for protein structure analysis', Journal of Biomolecular NMR, vol. 47, no. 2, pp. 143-153.
- Mouradov, D, Kobe, B, Dixon, N et al 2010, 'Hybrid methods for protein structure prediction', in H. Rangwala and G. Karypis (ed.), Introduction to Protein Structure Prediction, John Wiley & Sons Inc, Hoboken, NJ, pp. 265-277.
- Li, R, Ding, T, Huber, T et al 2009, 'Terahertz Time-Domain Spectroscopy of Peptides in Solution', International Conference on Infrared, Millimeter, and Terahertz Waves (IRMMW-THz 2009), Institute of Electrical and Electronics Engineers (IEEE Inc), Korea, pp. 1-2.
- Kobe, B, Guncar, G, Buchholz, R et al 2009, 'The Many Faces of Platelet Glycoprotein Ibα - Thrombin Interaction', Current Protein and Peptide Science, vol. 10, no. 6, pp. 551-558.
- Li, S, Mouradov, D, King, G et al 2009, 'Study of protein three-dimensional structure and dynamics using peptide amide hydrogen/deuterium exchange mass spectrometry (DXMS) and chemical cross-linking with mass spectrometry to constrain molecular modeling', in Gu J, Bourne P (ed.), Structural Bioinformatics (2nd ed), Wiley-Blackwell, United States, pp. 171-206.
- Robin, G, Cowieson, N, Guncar, G et al 2008, 'A General Target Selection Method for Crystallographic Proteomics', in Kobe B, Guss M, Huber T (ed.), Structural Proteomics: High Throughput Methods, Humana Press Inc., Totowa, NJ, USA, pp. 27-37.
- Mouradov, D, King, G, Ross, I et al 2008, 'Protein Structure Determination Using a Combination of Cross-Linking, Mass Spectrometry, and Molecular Modeling', in Kobe B, Guss M, Huber T (ed.), Structural Proteomics: High Throughput Methods, Humana Press Inc., Totowa, NJ, USA, pp. 459-477.
- Kobe, B, Guss, J & Huber, T, eds, 2008, Structural Proteomics, Humana Press Inc., Totowa, NJ, USA.
- Meng, W, Forwood, J, Guncar, G et al 2008, 'Overview of the Pipeline for Structural and Functional Characterization of Macrophage Proteins at the University of Queensland', in Kobe B, Guss M, Huber T (ed.), Structural Proteomics: High Throughput Methods, Humana Press Inc., Totowa, NJ, USA, pp. 577-589.
- Su, X, McAndrew, K, Huber, T et al. 2008, 'Lanthanide-Binding Peptides for NMR Measurements of Residual Dipolar Couplings and Paramagnetic Effects from Multiple Angles', Journal of the American Chemical Society, vol. 130, no. 5, pp. 1681-1687.
- Saunders, N, Brinkworth, R, Huber, T et al 2008, 'Predikin and PredikinDB: a computational framework for the prediction of protein kinase peptide specificity and an associated database of phosphorylation sites', BMC Bioinformatics, vol. 9, pp. 245:1-11.
- Su, X, Man, B, Beeren, S et al. 2008, 'A Dipicolinic Acid Tag for Rigid Lanthanide Tagging of Proteins and Paramagnetic NMR Spectroscopy', Journal of the American Chemical Society, vol. 130, no. 32, pp. 10486-10487.
- King, G, Jones, A, Kobe, B et al 2008, 'Identification of Disulfide-Containing Chemical Cross-Links in Proteins Using MALDI-TOF/TOF-Mass Spectrometry', Analytical Chemistry, vol. 80, no. 13, pp. 5036-5043.
- Cowieson, N, King, G, Cookson, D et al 2008, 'Cortactin Adopts a Globular Conformation and Bundles Actin into Sheets', Journal of Biological Chemistry, vol. 283, no. 23, pp. 16187-16193.
- Song, J, Yuan, Z, Tan, H et al 2008, 'Predicting disulfide connectivity from protein sequence using multiple sequence feature vectors and secondary structure', Bioinformatics, vol. 23, no. 23, pp. 3147-3154.
- Schmitz, C, Stanton-Cook, M, Su, X et al. 2008, 'Numbat: an iteractive sotware tool for fitting Δχ-tensors to molecular coordinates using pseudocontact shifts', Journal of Biomolecular NMR, vol. 41, no. 3, pp. 179-189.
- Kobe, B, Guncar, G, Buchholz, R et al 2008, 'Crystallography and protein-protein interactions: biological interfaces and crystal contacts', Biochemical Society Transactions, vol. 36, no. 6, pp. 1438-1441.
- Hadler, K, Huber, T, Cassady, A et al 2008, 'Identification of a non-purple tartrate-resistant acid phosphatase: an evolutionary link to Ser/Thr protein phosphatases?', BMC Research Notes, vol. 1, no. 78, pp. 1-8.
- Forwood, J, Thakur, A, Guncar, G et al 2007, 'Structural basis for recruitment of tandem hotdog domains in acyl-CoA thioesterase 7 and its role in inflammation', PNAS - Proceedings of the National Academy of Sciences of the United States of America, vol. 104, no. 25, pp. 10382-10387.
- Flanagan, J & Huber, T 2007, 'Structural Evolution of the ABC transporter Subfamily B', Evolutionary Bioinformatics, vol. 3, pp. 309-316.
- John, M, Schmitz, C, Park, A et al. 2007, 'Sequence-Specific and Stereospecific Assignment of Methyl Groups Using Paramagnetic Lanthanides', Journal of the American Chemical Society, vol. 129, no. 44, pp. 13749-13757.
- Su, X, Huber, T, Dixon, N et al. 2006, 'Site-Specific Labelling of Proteins with a Rigid Lanthanide-Binding Tag', ChemBioChem, vol. 7, no. 10, pp. 1599-1604.
- Mouradov, D, Craven, A, Forwood, J et al 2006, 'Modelling the structure of latexin-carboxypeptidase A complex based on chemical cross-linking and molecular docking', Protein Engineering Design and Selection, vol. 19, no. 1, pp. 9-16.
- Schmitz, C, John, M, Park, A et al. 2006, 'Efficient χ-tensor determination and NH assignment of paramagnetic proteins', Journal of Biomolecular NMR, vol. 35, no. 2, pp. 79-87.
- DeSantis, T, Hugenholtz, P, Larsen, N et al 2006, 'Greengenes, a Chimera-Checked 16S rRNA Gene Database and Workbench Compatible with ARB', Applied and Environmental Microbiology, vol. 72, no. 7, pp. 5069-5072.
- Song, J, Burrage, K, Yuan, Z et al 2006, 'Perdiction of cis/trans isomerization in proteins using PSI-BLAST profiles and secondary structure information', BMC Bioinformatics, vol. 7, no. 124, pp. 1-13.
- Puri, M, Robin, G, Cowieson, N et al 2006, 'Focusing in on structural genomics: The University of Queensland structural biology pipeline', Biomolecular Engineering (till 2008), vol. 23, no. 6, pp. 281-289.
- Aagaard, A, Listwan, P, Cowieson, N et al 2005, 'An Inflammatory Role for the Mammalian Carboxypeptidase Inhibitor Latexin: Relationship to Cystatins and the Tumour Suppressor TIG1', Structure, vol. 13, no. 2, pp. 309-317.
- Cowieson, N, Listwan, P, Kurz, M et al 2005, 'Pilot studies on the parallel production of soluble mouse proteins in a bacterial expression system', Journal of Structural and Functional Genomics, vol. 6, no. 1, pp. 13-20.
- Ozawa, K, Headlam, M, Mouradov, D et al 2005, 'Translational incorporation of L-3,4-dihydroxyphenylalanine into proteins', The FEBS Journal, vol. 272, no. 12, pp. 3162-3171.
- Potapov, A, Yagi, H, Huber, T et al 2010, 'Nanometer-Scale Distance Measurements in Proteins Using Gd3+ Spin Labeling', Journal of the American Chemical Society, vol. 132, no. 26, pp. 9040-9048.
- Huber, T & Torda, A 2002, 'Protein structure prediction by threading: Force field philosophy, approaches to alignment.', in Igor F. Tsigelny (ed.), Protein Structure Prediction: Bioinformatic Approach, International University Line, La Jolla, California, USA, pp. 263-296.
- Xu, Y, Carr, P, Huber, T et al. 2001, 'The structure of the PII-ATP complex', European Journal of Biochemistry, vol. 268, no. 7, pp. 2028-2037.
- Reith, D, Huber, T, Mueller-Plathe, F et al. 2001, 'Free energy approximations in simple lattice proteins', Journal of Chemical Physics, vol. 114, no. 11, pp. 4998-5005.
- Abraham, M, Procter, J, Huber, T et al. 2001, 'Protein folding force fields: Optimisation and optimism', Biomedical Research in 2001, ed. Brian Lithgow and Irena Cosic, Monash University, Clayton, Victoria, pp. 111-114.
- Rendell, A, Bliznyuk, A, Huber, T et al 2000, 'Computational chemistry on Fujitsu vector-parallel processors: Development and performance of applications software', Parallel Computing, vol. 26, pp. 887-911.
- Huber, T & Torda, A 1999, 'Protein sequence threading, the alignment problem and a two step strategy', Journal of Computational Chemistry, vol. 20, pp. 1455-1467.
- Ayers, D, Huber, T & Torda, A 1999, 'Protein fold recognition force fields: unusual construction strategies', Proteins: Structure Function and Genetics, vol. 36, pp. 454-461.
- Scott, W, Hunenberger, P, Tironi, I et al 1999, 'The GROMOS biomolecular simulation program package', Journal of Computational Chemistry, vol. 103, pp. 3596-3607.
- Huber, T, Russell, A, Ayers, D et al 1999, 'Sausage: protein threading with flexible force fields', Bioinformatics, vol. 15, pp. 1064-1065.
Projects and Grants
Grants information is drawn from ARIES. To add or update Projects or Grants information please contact your College Research Office.
- Enhanced high-field nuclear magnetic resonance spectroscopy (Secondary Investigator)
- Methods for Protein Structure Analysis by Electron Paramagnetic Resonance (Primary Investigator)
- New methods for drug discovery by NMR spectroscopy (Primary Investigator)
- Ultrafast magic angle spinning solid-state NMR capability (Secondary Investigator)
- Decrypting the Excitation Contraction coupling machinery in skeletal muscle (Secondary Investigator)
- New methods for protein design (Secondary Investigator)
- Tags and algorithms for studies of protein structures and interactions (Primary Investigator)
- 3D structure determination of biomolecular assemblies from sparse data of different length scales (Primary Investigator)
- Mapping protein contacts and conformational changes in macromolecular assemblies (Secondary Investigator)
- 3D Structure determination of biomacromolecular assemblies from sparse data (Primary Investigator)
- New fragment-based drug design technology by NMR spectroscopy (Secondary Investigator)